The applicant laboratory has recently identified a unique protein kinase system which is in high levels in several rapidly proliferating mammalian cell systems. This protein kinase system is stimulated by polycations (e.g., spermine, spermidine, putrescine, polylysine, histones, etc.) and phosphorylates both tightly enzyme-bound endogenous proteins and non-bound low molecular weight endogenous proteins. Protein kinases are the well established terminal enzymatic components of the system of cyclic nucleotides (cyclic AMP and cyclic GMP) which regulates processes of cellular growth and differentiation. Polyamines are also key regulators of cellular growth and differentiation, and they are are elevated in rapidly proliferating mammalian cell systems. Initial comparsions of the polyamine "responsive" protein kinase system in non-proliferating versus proliferating rat liver tissues show several major differences. It is proposed to: 1) purify the polyamine stimulatable protein kinase from non-proliferating adult rat liver, from intermediate rate growing Morris hepatoma #7800, and from rapidly growing Morris hepatoma #3924A; 2) separate and compare catalytic moieties and enzyme-bound endogenous substrate proteins from each tissue by kinetic and physical protein methodologies; 3) identify, isolate, and purify the non-enzyme-bound endogenous substrate proteins from each tissue. The proposed study will evaluate the role of protein kinase phosphorylation in the polyamine regulation of cellular growth. It is likely that the two cellular regulatory systems, cyclic nucleotides and polyamines, utilize a common enzyme system, a polyamine-responsive protein kinase. The proposed study will evaluate this possibility.